Dr. Holroyd proposes to investigate the genetic control of bronchial hyperresponsiveness (BHR) an IgE levels in human populations. We have recently localized major gene(s) that regulates BHR and total serum IgE to chromosome 5q. Linkage analyses suggest these genes are located near important immunoregulatory candidate genes that participate in controlling IgE levels. These findings represent a major step in mapping genes important in the regulation of allergic and asthmatic responses and delineating their role in the pathogenesis of allergic asthma. The major objectives of Dr. Holroyd's proposal are to further define and extend the preliminary genetic linkage findings. He will first attempt to narrow our localization of these genes in allergic asthma using linkage analysis. Known immunoregulatory genes, as well as other expressed sequences, will be localized on a physical map of chromosome 5q. He will also carry out a definitive examination of the DNA sequence from likely gene candidates for mutations in allergic asthmatics as compared to controls. These studies will provide useful new polymorphisms and potential mutations that can be examined by us and other investigators studying different populations for allergy and asthma.